The proposed project studies a centrally important question in substance use research-namely, how is risk transmitted across multiple generations? First, we follow children of alcoholics (COAs) and controls into adulthood to examine risk for persistent and developmentally limited substance use/abuse, and to identify mediating mechanisms underlying this risk. Second, we examine emerging risk in the next generation using a multi-method laboratory study of reactivity and regulation as mediators of familial alcoholism risk in the young children of our subjects. We examine co-transmission of risk and risk mediators, and we examine the role of parenting in mediating and modifying this risk. To achieve these aims, we propose a follow-up of our sample (at ages 23-30) and a laboratory study of their young children. The sample is drawn from the community, and includes alcoholic mothers and fathers, and both active" and "remitted" alcoholics. Parent alcoholism and other disorders were directly ascertained, and multiple reporter data minimize the impact of response biases. Beginning in adolescence (M=12.7 years), subjects and their parents received 3 annual computer-assisted interviews. A 4th assessment (now including full biological siblings and peer informants) occurred during the transition from late adolescence to adulthood (ages 18-25). At the proposed follow-up, computer-assisted interviews and psychophysiological assessments will be conducted with the adult subjects. Informant data will be collected in mailed surveys. The young children of our subjects will be assessed with multiple methods, including psychophysiological responses, facial expression, behavioral observation, and multiple informant reports of reactivity and regulation, as well as markers of risk for later substance abuse (conduct problems, social competence, ego-resilience and academic achievement). Data analytic strategies include multilevel modeling for modeling observations clustered within families over time. The findings will be particularly useful for prevention because they focus on a high risk group, they track the natural history of substance use from its precursors to clinically important end points, they include potentially modifiable factors, and they examine the transmission of risk across three generations.